Synthesis of 3-Aminobenzisoxazoles Using an Electrophilic Aminating Reagent

Organic Letters 2026

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Authors: Jacob W. Baer, Gary M. Gallego, Rebecca A. Gallego, Madeline Berry, John Braganza, Doris Chen, James L. Collins, Jacob C. DeForest, Joyann S. Donaldson, Christiana S. Park, Stephanie Scales, G SMITH
+7 more Khanh Tran, Raymond K. Twumasi, F. Wang, Natalie Zachariou, Neal W. Sach, Louise Bernier, Alexander Burtea
DOI: 10.1021/acs.orglett.5c05009
Cited by: 3
References: 21

Abstract

Aminobenzisoxazoles are important scaffolds in medicinal chemistry. Traditionally, these heterocycles have been synthesized from 2-fluorobenzonitriles and N-protected hydroxylamines via the S N Ar reaction and subsequent cyclization. We have developed a novel, orthogonal method that utilizes 2-hydroxybenzonitriles with O -(diphenylphosphoryl)hydroxyl amine as an electrophilic nitrogen source. This approach inverts the traditional polarity (making the arene the nucleophile) and allows for mild reaction conditions, a broad substrate scope, and extension to a few other heterocycles.

Fields of Study & Subjects

Catalytic C–H Functionalization Methods Catalytic Cross-Coupling Reactions Advanced Synthetic Organic Chemistry

Publication details

Journal / source
Organic Letters
Publisher
American Chemical Society (ACS)
Volume
28
Issue
3
Pages
1015–1018
Publication date
9 January 2026
Language
EN